TAK1 in the AP-1 pathway is a critical target of Saururus chinensis (Lour.) Baill in its anti-inflammatory action.

ETHNOPHARMACOLOGICAL RELEVANCE: Saururus chinensis (Lour.) Baill (Saururaceae), also known as Asian lizard's tail, is a plant commonly found in East Asia. Its leaves have been used in traditional medicine to treat many diseases such as edema, pneumonia, hypertension, leproma, jaundice, gonorrhea, and rheumatoid arthritis. AIM OF THE STUDY: Based on the efficacies of S. chinensis, the anti-inflammatory effects of this plant and the molecular mechanism were evaluated using the ethanol extract of S. chinensis leaves (Sc-EE). MATERIALS AND METHODS: The production of pro-inflammatory mediators and cytokines in response to Sc-EE was evaluated using Griess and semi-quantitative reverse transcription-polymerase chain reactions. Furthermore, relevant proteins including c-Jun, c-Fos, p38, JNK, ERK, MEK1/2, MKK3/6, MKK4/7, and TAK1 were detected through immunoblotting. RESULTS: Sc-EE diminished production of nitric oxide (NO); decreased expression levels of cyclooxygenase (COX)-2, interleukin (IL)-6, inducible NO synthase (iNOS), and IL-1ß in LPS-stimulated RAW264.7 cells; and attenuated activator protein 1 (AP-1)-mediated luciferase activities. The extract markedly downregulated the phosphorylation of TAK1, upregulated thermal stability of TAK1, and reduced TAK1/AP-1-mediated luciferase activity in LPS-treated RAW264.7 cells and TAK1-overexpressing HEK293T cells. CONCLUSIONS: These results demonstrated that Sc-EE suppresses pro-inflammatory gene expression through blockade of the TAK1/AP-1 pathway in LPS-treated RAW264.7 macrophages, implying that inhibition of TAK1/AP-1 signaling by S. chinensis is a key event in its anti-inflammatory activity.

Dibenzylbutane neolignans from Saururus cernuus L. (Saururaceae) displayed anti-Trypanosoma cruzi activity via alterations in the mitochondrial membrane potential.

The MeOH extract from leaves of Saururus cernuus L. (Saururaceae) displayed in vitro activity against trypomastigote forms of T. cruzi (100% of parasite death at 200 µg/mL), suggesting the presence of bioactive compounds. Thus, the bioactivity-guided fractionation was carried out, leading to the isolation of three related neolignan derivatives, identified as threo-austrobailignan-5 (1), threo-austrobailignan-6 (2), and threo-dihydroguaiaretic acid (3). Anti-T. cruzi activity of compounds 1-3 was performed against cell-derived trypomastigotes and intracellular amastigotes. Additionally, the mammalian cytotoxicity was investigated using NCTC cells. Compound 2 was the most effective against extracellular trypomastigotes with IC50 of 3.7 µM, while compound 3 showed activity in both clinically relevant forms of the parasite, trypomastigotes and amastigotes, with IC50 values of 7.0 and 16.2 µM, respectively. However, the structurally related compound 1 was inactive. Based on these results, compounds 2 and 3 were selected to evaluate the mechanism of cellular death. Compound 2 induced alteration in the plasma membrane permeability and consequently in the ROS levels after 120 min of incubation. By using flow cytometry and fluorescence microscopy, compound 3 showed alterations in the mitochondrial membrane potential (ΔΨm) of trypomastigotes. Considering the promising chemical and biological properties of neolignans 2 and 3, these compounds could be used as starting points to develop new lead compounds for Chagas disease.

Lignans from Saururus chinensis exhibit anti-inflammatory activity by influencing the Nrf2/HO-1 activation pathway.

As part of our ongoing program to develop anti-inflammatory agents, an extract derived from Saururus chinensis collected in Korea was found to inhibit nitric oxide (NO) production in RAW264.7 cells. Bioassay-guided fractionation led to the isolation two new (1 and 2) and six known dineolignans (3-8). To the best of our knowledge, manassatin B1 (3) was isolated from S. chinensis for the first time. All structures were elucidated using extensive spectroscopic analysis. Of these compounds, 2 and 8 inhibited lipopolysaccharide (LPS)-induced production of NO and showed IC50 values of 5.80 and 1.52 µM, respectively. LPS-induced expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) was also significantly suppressed by the administration of 2 and 8. In addition, these lignans induced the expression of heme oxygenase-1 (HO-1) in a concentration-dependent manner. Nuclear translocation of nuclear-E2-related factor 2 (Nrf2), a key regulator of HO-1 protein expression, was also induced in RAW264.7 cells treated with 2 and 8. These findings suggested that these lignans exerted anti-inflammatory effects in RAW264.7 cells through modulation of the Nrf2/HO-1 pathway and that they were potential HO-1 inducers for preventing or treating inflammation.

Two new lignans from Saururus chinensis.

Two new lignans, (Z)-14-bis(3',4'-dimethoxyphenyl)-2,3-dimethylbut-2-ene-1,4-dione (1), threo-2-methyl-3-oxo-1-(3',4',5'-trimethoxyphenyl)butyl-3″,4″-dimethoxybenzoate (2), together with 15 known derivatives (3-17) were isolated from Saururus chinensis. Their structures were determined on the basis of spectral data, including 1D and 2D NMR experiments and HREIMS spectra. The antitumour activity was screened by MTT assay, compounds 1, 2, 3, 5, 9-11 and 13-15 showed no cytotoxic activity against HL-60, SMMC-7721, A549, MCF-7 and SW480 cell lines.

Sauruchinenols A and B, unprecedented monocyclic diterpenes with new carbon skeleton from the aerial parts of Saururus chinensis.

Sauruchinenols A (1) and B (2), two novel monocyclic diterpenes with unique carbon skeleton, as well as two new structurally related diterpenes, sauruchinenols C (3) and D (4), were isolated from the aerial part of Saururus chinensis. Their structures were elucidated based on the analysis of spectroscopic data. A hypothetical biogenetic pathway for sauruchinenols A and B was proposed.

Two new lignans from Saururus chinensis and their DGAT inhibitory activity.

Two new lignans were isolated from Saururus chinensis, along with eight known compounds. Their structures were elucidated on the basis of spectroscopic and physico-chemical analyses. All the isolates were evaluated for in vitro inhibitory activity against DGAT1 and DGAT2. Among them, compounds 2, 3, 5 and 7 were found to exhibit selective inhibitory activity on DGAT1 with IC50 values ranging from 44.3±1.5 to 87.5±1.3µM.

Houttuynia cordata alleviates high-fat diet-induced non-alcoholic fatty liver in experimental rats.

CONTEXT: Houttuynia cordata Thunb. (Saururaceae) is used traditionally in Asian countries to treat various disease symptoms. OBJECTIVE: To study the effect of H. cordata ethyl acetate (HC-EA) extract on high-fat diet (HFD)-induced hepatic steatosis. MATERIALS AND METHODS: HFD fed rats were orally dosed with HC-EA (100, 200, or 300 mg/kg) once daily for 8 weeks and the lipid profiles and protein expressions in hepatocytes were evaluated. RESULTS: HFD rats showed an increase (p < 0.05) in the plasma lipid levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), free fatty acids (FFAs), and reduced the high-density lipoprotein (HDL) levels. Treatment with HC-EA extract (300 mg/kg) restored the changes in plasma lipid levels of TC, TG, LDL, FFA, and HDL in HFD-fed rats by 34.8, 31.1, 51.4, 32.4, and 56.3%, respectively, compared with control rats (p < 0.01). HC-EA treatment also decreased the hepatic lipid accumulation (p < 0.001 at 300 mg/kg) and improved hepatic histological lesions. HC-EA extract enhanced AMPK phosphorylation and its primary downstream targeting enzyme, acetyl-CoA carboxylase (ACC), up-regulated the gene expression of carnitine palmitoyl transferase-1 (CPT-1), and down-regulated sterol regulatory element binding protein 1, fatty acid synthase, and glutamate pyruvate transaminase protein levels in the livers of HFD-fed rats. Further, the increased expression of hepatic cytochrome P450 (CYP) composition such as CYP2E1 and CYP4A was also suppressed. DISCUSSION AND CONCLUSION: Data suggest that HC-EA extract might act by regulating the AMPK-dependent pathway and related mediators and might be used in treating obesity-related liver diseases.

A current update on the phytopharmacological aspects of Houttuynia cordata Thunb.

The present review is an attempt to put an insight into a medicinal plant Houttuynia cordata Thunb, which is indigenous to North-East India and China. It is an aromatic medicinal herb belonging to family Saururaceae and is restricted to specialized moist habitats. The review provides detailed information regarding the morphology, distribution, phytochemistry, ethnopharmacological uses and also describes various pharmacological activities reported on the plant H. cordata. The review describes therapeutic efficacy of the whole plant and its extracts, fractions and isolated compounds in different diseased condition. Among the important pharmacological activities reported includes, anti-mutagenic, anti-cancer, adjuvanticity, anti-obesity, hepatoprotective, anti-viral, anti-bacterial, anti-inflammatory, free radical scavenging, anti-microbial, anti-allergic, anti-leukemic, chronic sinusitis and nasal polyps activities. Thus, the present review will act as a source of referential information to researchers to perform clinical studies on isolated compounds that may serve the society and will help in improving human health care system.

Anticestodal activity of Houttuynia cordata leaf extract against Hymenolepis diminuta in experimentally infected rats.

The leaves of Houttuynia cordata Thunb. (Saururaceae) are considered to have anthelmintic properties in the traditional medicine of Naga tribes in Northeast India and, therefore, are used by the natives to treat the intestinal worm infections. In the present study, the anticestodal activity of H. cordata leaf extract was investigated against Hymenolepis diminuta, a zoonotic cestode, in experimentally infected albino rats. For the assessment of anticestodal efficacy, the eggs per gram (EPG) of faeces counts and worm loads of animals were monitored following treatment with 200, 400 and 800 mg/kg p.o. doses of leaf extract to different groups of rats harbouring larval, immature and mature H. diminuta infections. The efficacy of the extract was found to be dose-dependent (P < 0.05). Further, the extract showed its maximum efficacy against the mature Hymenolepis worms. In this case, the 800 mg/kg dose of extract significantly reduced (P < 0.001) the EPG counts of animals by 57.09% and worm load by 75.00%, at post-treatment. In comparison, the reference drug praziquantel at 5 mg/kg showed a reduction in the EPG counts and worm load of experimental animals by 80.37 and 87.50%, respectively. These findings indicate that leaves of H. cordata possess significant anticestodal property and provide a rationale for their use in traditional medicine as an anthelmintic.